Documenta Ophthalmologica最新文献

Purpose: The clinical electrooculogram (EOG) is used for the diagnosis of bestrophinopathies to evaluate the function of the retinal pigment epithelium. The current ISCEV test protocol uses a broad band white light with luminance of 100 cd/m². An alternative monochromatic 448 nm short wavelength (SW-EOG) has been proposed but to date has not been evaluated in clinical cases where the standard EOG is abnormal.

Methods: To evaluate the clinical potential of the SW-EOG four genetically confirmed cases of Best Vitelliform Macular Dystrophy were tested using the standard white (100 cd/m²) and SW-EOG (448 nm) at 30 cd/m² to ascertain if the SW-EOG was also affected. In addition, a qualitative 5-point Likert survey was conducted to gauge overall patient comfort.

Results: In all four cases the SW-EOG was reduced and provided an equivalent clinical measure for RPE dysfunction. All four participants rated the SW-EOG as being more comfortable than the white standard EOG test.

Conclusions: This is the first demonstration of an alternative stimulus for the EOG that provided clinically valid results with greater comfort than the current ISCEV protocol. Further studies are required to validate the SW-EOG as an alternative to the white broad band stimulus.

Background: Recording electroretinograms (ERGs) in eyes with intraocular gas tamponade is difficult, and the mechanism remains unclear. We evaluated the effect of intraocular gas on ERGs by comparing recordings at different body positions.

Methods: This study included 31 patients who underwent vitrectomy with sulfur hexafluoride (SF6) or air tamponade at Hirosaki University (between May 2023 and October 2024). The patients included those with retinal detachment (25 patients), macular holes (4 patients), and epiretinal membranes (2 patients). ERGs were recorded using skin electrodes when approximately 50% of the vitreous cavity was filled with the intraocular gas. ERGs were recorded in sitting, supine, and face-down positions. Amplitudes and latencies of the LA 3 b-wave and LA 30 Hz were compared using the Wilcoxon signed-rank and Friedman tests.

Results: In the gas-filled eyes, amplitudes in the face-down position were smaller, and latencies were longer than those in the other positions (p < 0.05). Median amplitudes in the gas-filled eyes in the sitting, supine, and face-down positions were 20.4, 19.5, and 10.1 µV for LA 3 and 14.4, 15.5, and 7.11 for LA 30 Hz, respectively; median latencies were 32.5, 33.0, and 34.3 ms for LA 3 and 30.8, 30.0, and 34.3 for LA 30 Hz, respectively.

Conclusions: ERG amplitudes were reduced and latencies were prolonged in the face-down position, which may be attributed to a larger retinal area being covered by intraocular gas. The gas acts as an insulator, and the gas-covered retina may not effectively generate or transmit electrical signals.

Objective: To evaluate full-field electroretinogram (ffERG) parameters and evaluate their clinical associations in patients with acute Vogt-Koyanagi-Harada (VKH) disease over a 4-year follow-up.

Methods and analysis: This retrospective cohort study included 21 patients with acute VKH disease followed for 48 months after initiation of systemic corticosteroid therapy, with or without adjunctive immunosuppression. ffERG was performed at 1, 6, 12, and 48 months (M) post-treatment. At M48, eyes were classified into two groups: Group 1 (normal ffERG) and Group 2 (subnormal ffERG), based on whether any ffERG parameters fell below the 5th percentile of age-matched healthy controls. Main outcomes included longitudinal ffERG changes, clinical associations, and the 6-month recovery ratios relative to baseline (M1).

Results: All ffERG parameters improved significantly from baseline to M6 (p < 0.001) and to M12 (p < 0.001) and stabilized thereafter. Group 2 exhibited consistently reduced ffERG amplitudes compared to Group 1 throughout follow-up (p < 0.01 to p < 0.001), despite similar recovery trends. Recovery ratios at M6 ranged from 27%-78% in Group 1 and 26%-175% in Group 2; however, Group 2 remained below normal levels at M48. Sunset glow fundus (SGF) at M12 was significantly more frequent in Group 2 (60.7%) than in Group 1 (21.4%, p = 0.025).

Conclusions: Retinal function improved during the first year and stabilized thereafter, irrespective of treatment type. Persistent subnormal ffERG at 48 months reflected a poorer baseline function and was associated with the development of SGF.

Purpose: We present a rare case of a 25-year-old Polish male diagnosed with rhegmatogenous retinal detachment (RRD) on a background of gyrate atrophy (GA), successfully treated with pars plana vitrectomy (PPV) combined with cryotherapy and perfluoropropane (C3F8) gas tamponade.

Methods: Regular ophthalmic examinations with optical coherence tomography were performed preoperatively and three months postoperatively.

Results: The patient initially presented with acute loss of vision to counting fingers in the left eye secondary to a macula-off RRD. Intraoperatively, multiple circumferential skirts of vitreous bands and a peripheral break at 11 o'clock were identified. The break was treated with cryotherapy and C3F8 gas tamponade. The patient underwent left-sided cataract surgery six months following his vitrectomy and subsequently a YAG laser posterior capsulotomy. The retina remained attached at his 9-month follow up with a final best-corrected visual acuity of 6/9-1.

Conclusions: PPV with cryotherapy and perfluoropropane tamponade can be an effective surgical approach in the management of RRD with underlying GA. Compared to previously reported cases, a favourable visual outcome was achieved in our case, likely attributed to the absence of other ophthalmic complications (such as proliferative vitreoretinopathy) and timely surgical intervention. Recognising atypical vitreous characteristics intraoperatively may refine surgical techniques and outcomes in similar cases. Future cases could consider an encircling scleral band for additional support, particularly in cases involving inferior retinal breaks.

Purpose: To report the clinical phenotype, imaging characteristics, and electrophysiologic findings of a 62-year-old patient with retinitis pigmentosa (RP) harboring a likely pathogenic homozygous KIZ (NM_018474.6) start codon variant (c.3G > A, p.Met1?), only previously reported in the compound heterozygous state.

Methods: The patient underwent clinical evaluation including full medical history, best-corrected visual acuity (BCVA), slit lamp exam, and dilated fundus examination (DFE), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinography (ffERG), following the ISCEV standard protocols. Genetic testing was performed using the Invitae inherited retinal disorders panel of 330 genes.

Results: BCVA was 20/40 in both eyes. Fundus examination revealed mild optic disc pallor, arteriolar attenuation, peripheral pigment migration, and macular hyper-autofluorescence along the arcades. with macular sparing. Outside the arcades, there are hypo-autofluorescence spots corresponding to retinal pigement epithelium atrophy. There is marked peri-papillary atrophy. SD-OCT showed diffuse outer retinal thinning, ellipsoid zone constriction, mild cystoid macular edema, and epiretinal membrane. ffERG was consistent with a rod-cone dystrophy, with extinguished dark-adapted responses and severely attenuated 30 Hz flicker amplitudes. Genetic testing identified a heterozygous variant of uncertain significance in CTNNA1 (c.1486C > T, p.Arg496Cys) and a homozygous KIZ variant (c.3G > A, p.Met1?), previously observed only in compound heterozygosity. The patient was diagnosed with KIZ-associated RP and initiated on topical dorzolamide.

Conclusions: This case expands the clinical spectrum of KIZ-associated RP by describing the phenotype associated with a homozygous start codon variant. Despite the disruptive nature of the mutation, the patient exhibited a relatively mild rod-cone dystrophy with retained cone responses into the seventh decade. These findings support the inclusion of KIZ in diagnostic panels for autosomal recessive RP and contribute valuable genotype-phenotype correlation data for this rare ciliopathy.

Purpose: To compare pupillary responses during two-color light stimulation and the post-illumination pupillary response (PIPR) between patients with Leber hereditary optic neuropathy (LHON) and established optic atrophy and patients with primary open-angle glaucoma (POAG) who have central visual dysfunction with similar magnitude to that of the LHON patients.

Methods: Fourteen normal controls, eight patients with POAG and mean deviation of the Humphrey visual field and circumpapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thickness measured using optical coherence tomography being comparable to those of LHON patients, and nine patients with LHON were included. Using a handheld electronic pupillometer, pupil diameter of the eye contralateral to the stimulation was recorded during a 7 s baseline period, a 10 s red light stimulation followed by a 40-s post-stimulation period, and a 10 s blue light stimulation followed by a 40 s post-stimulation period.

Results: The ratio of pupil diameter at 6 s after blue, but not red, light offset as well as the subtraction of difference between the baseline pupil diameter and the mean pupil diameter during the 30 s post-illumination using red stimulus from the counterpart using blue stimulus was significantly larger in POAG patients than in the other two groups. The maintenance of pupillary constriction during blue light stimulation was significantly reduced in POAG patients compared with the other two groups.

Conclusions: Compared with POAG patients who had comparable macular structural and functional damage, LHON patients showed better pupillary responses during blue light stimulation and PIPR, reflecting preserved ipRGC function.

Purpose: To describe a new method to visualize the amplitude profile of light adapted ERGs as a series of contour plots in response to a Flash Strength series.

Methods: Light adapted ERGs from a dataset of n = 88 Autism Spectrum Disorder (ASD) and n = 70 typically developing Control participants were used incorporating 10 flash strengths ranging from 12 to 446 Troland seconds (Td.s). The region chosen for analysis included the baseline, a-wave and ascending limb of the b-wave and included n = 1736 control and n = 1300 ASD waveforms. A Generalized Additive Model (GAM) with complexity penalized tensor product splines was applied to the waveform intervals.

Results: Contour plots derived from the ASD and Control groups revealed a pattern of reduced amplitude in the ascending limb of the b-wave for the ASD group. Representative responses were derived from the GAM model for discrete Flash Strengths to exemplify the changing profile of the ERG waveform. A contour plot of the derived z-scores provided a qualitative evaluation of the differences in the mean amplitudes which was concentrated on the b-wave.

Conclusions: The production of contour plots based on amplitude, time and Flash Strength with minimal a priori assumptions provide an additional approach to analyzing stimulus response data series and may support clinical applications. Additionally, the GAM-based methodology provides a tool for simultaneous investigation of the amplitude changes over time and Flash Strength which can be useful for theoretical purposes.

Purpose: To characterize the clinical phenotype associated with a homozygous start codon-altering complex variant in the ABCA4 gene and evaluate its severity and prognosis in the context of Stargardt disease.

Methods: Patient records were retrospectively reviewed for homozygous ABCA4 start codon variants. Patients underwent ophthalmic exam, multimodal imaging, full-field electroretinography (ffERG), and inherited retinal disease panel testing. Structural and functional retinal assessments were reviewed to determine phenotype severity.

Results: Three brothers of Ashkenazi Jewish descent presented with profound early-onset vision loss beginning at age 7, with best-corrected visual acuity reduced to counting fingers or hand motion by early adulthood. Imaging revealed widespread macular atrophy, extensive intraretinal pigment migration, and near-complete foveal outer nuclear layer loss. ffERG demonstrated extinguished scotopic and photopic responses. The patients were found to be homozygous for a complex ABCA4 allele containing the start codon variant c.[1A > G;6089G > A]. These features were consistent with the rapid-onset chorioretinopathy phenotype, previously associated with null ABCA4 alleles.

Conclusions: This report characterizes the clinical findings in patients homozygous for the c.[1A > G;6089G > A] variant in ABCA4, confirming its association with a severe, rapid-onset chorioretinopathy phenotype. The data support the pathogenic nature of this complex allele and expands the genotype-phenotype correlational spectrum of ABCA4-related disease, with implications for prognosis and genetic counseling.

Purpose: We report the clinical history of two siblings, initially diagnosed with juvenile glaucoma (JG), who were subsequently found to harbor a novel pathogenic OPA1 splicing variant consistent with dominant optic atrophy (DOA).

Methods and results: The male proband presented with elevated intraocular pressure (IOP) at age 11, while his sister had normal IOP values at age 16. Both developed bilateral temporal optic nerve pallor, central visual field defects, and reduced color vision. Optical coherence tomography (OCT) confirmed thinning of the retinal nerve fiber and ganglion cell layers. Whole exome sequencing identified a novel splice-site variant in OPA1 (NM_130837.3:c.611-2A>T) in both siblings and their affected mother, classified as pathogenic according to ACMG/AMP guidelines. During treatment washout, the male proband showed elevated IOP, consistent with concomitant JG and DOA, whereas the sister exhibited DOA only.

Conclusions: This report highlights the importance of considering DOA in young patients with presumed JG, and suggests potential overlapping pathophysiology involving mitochondrial dysfunction and retinal ganglion cells vulnerability.

Purpose: To report a case of α-mannosidosis with intellectual, hearing impairment and progressive retinal degeneration, supported by ten years of ophthalmic follow-up, genetic testing, and leukocyte α-mannosidase enzymatic analysis.

Methods: The patient underwent serial ophthalmic examinations over a ten-year period, including best-corrected visual acuity (BCVA) testing, fundus photography, optical coherence tomography (OCT), and fundus autofluorescence (FAF), to monitor disease progression. Trio-based whole-exome sequencing (WES) was performed on the family. Variant confirmation was conducted via Sanger sequencing. To support the genetic findings, leukocyte α-mannosidase activity was measured using fresh peripheral blood samples.

Results: At first presentation, BCVA was 20/50 OD and 20/40 OS. Over the next decade, vision progressively declined to 20/200 in both eyes. Fundus images showed granular pigment mottling in the posterior pole, and subsequent wide-angle imaging detected bone-spicule pigmentation deposits in peripheral retina. OCT demonstrated progressive retinal thinning, with loss of the ellipsoid zone. FAF revealed expanding areas of retinal atrophy. The patient has presented with bilateral sensorineural hearing loss, delayed speech development, persistent dysarthria, mild cognitive impairment, and coarse facial features since childhood. Genetic analysis identified a novel homozygous MAN2B1 mutation: c.1316_1327delinsTGATG (p.Ala439Valfs*36), inherited from consanguineous parents with the same heterozygous genotypes. The variant was classified as pathogenic based on ACMG criteria. The patient's leukocyte α-mannosidase activity was profoundly decreased, confirming the diagnosis.

Conclusions: This case highlights the progressive nature of retinal degeneration in α-mannosidosis and underscores the diagnostic value of leukocyte enzyme testing alongside genetic and ophthalmic assessments. Early recognition of ophthalmic signs, particularly in patients with syndromic features such as hearing loss and facial dysmorphism, is essential for timely diagnosis and intervention.